Activation of receptors for endogenous excitatory amino acids have been shown to bring about an increase in cGMP formation in cerebellum. We have now characterized the cGMP response to various excitatory decarboxylic amino acids in 8 day old primary cultures of rat cerebellar granule cells. This increase in cGMP content following the application of different excitatory amino acids to the cultures has been found to be dependent on the ionic component of the medium and Mg++ in particular. This observation will be a departure point to study the interactions among kainic acid, aspartate, and glutamate recognition sites at the cellular level, and to characterize whether kainic acid receptors have a physiological role or participate only in neurodegenerative disorders.